Menthol propyleneglycol-carbonate and analogs thereof as insect pest repellents

ABSTRACT

Menthol propyleneglycol-carbonate, analogs thereof and compositions containing such compounds are useful as insect repellents.

CROSS-REFERENCE TO RELATED APPLICATION

This application claims the benefit of U.S. Provisional Application No.60/500,392, filed Sep. 5, 2003.

BACKGROUND OF THE INVENTION

The present invention relates to the insect repellent effects of mentholpropyleneglycol-carbonate and analogs thereof.

Menthol is a natural product which is obtainable from peppermint oil andother mint oils. Menthol and various analogs thereof, such as(−)-isopulegol, N-ethyl-p-menthane-3-carboxyamide and p-methane-3,8diol, are used in commerce as cooling agents. These compounds impart acooling sensation to a variety of products, for example, cosmetics,perfumes, personal care products, oral hygiene products, confectionary,cigarettes, cough drops, nasal inhalants and the like. See, also U.S.Pat. No. 5,703,123 to Pelzer, et al.

Menthol has also been applied as a topical antipruitic, and inveterinary medicine as a mild local anesthetic and antiseptic, as wellas an internal carminative and gastric sedative. See also, U.S. Pat. No.5,124,320 to Ivy et al.

Menthol and various of its analogs have also been found to possessanti-fouling activity. See published International Patent ApplicationNo. PCT/01/40929.

Menthol has been disclosed as one of several components of a miticide inJP 4305505A, and as the essential constituent of a cockroach repellentin JP 55104202A.

Certain analogs and derivatives of menthol have also been disclosed aseffective repellents against noxious insects, such as mosquitoes, ticksand mites. These include p-menthane-3,8-diol, as described in U.S. Pat.No. 5,959,161 to Akiyama et al., and the menthyl ester ofpyrrolidone-5-carboxylic acid, as described in U.S. Pat. No. 6,451,884to Watkins et al.

Research into the effectiveness of naturally-occurring chemicalcompounds for use as insect repellents and in other applications hasbeen motivated, at least in part, by a growing public concern over thepossible health risks associated with products of this type that containsynthetic chemicals as active agents. Consequently, efforts continuetoward the development of safe and effective insect repellents based onnatural compounds.

SUMMARY OF THE INVENTION

It has now been discovered, in accordance with the present invention,that carbonic acid derivatives of menthol and various analogs thereofare very effective insect repellents.

In accordance with one aspect of the present invention, there isprovided a method for repelling insects from a site, which comprisesapplying to the site an insect repelling amount of a compound of theformula:

wherein R represents a straight or branched chain, substituted orunsubstituted lower alkyl radical, or a straight or branched chain,substituted or unsubstituted lower alkenyl radical; X represents acarbonyl linking group (—C(═O)—) or a valence bond;

-   n is 0 or 1; and-   R′ represents a radical selected from the group consisting of    substituted or unsubstituted hydroxyalkyloxy and substituted or    unsubstituted hydroxyalkyl, when n is 1; and R′ represents an    alkylamine radical when n is 0.

The method is effective for repelling insect pests from animals, e.g.humans and livestock, plants, plant parts, seeds and from inanimateobjects, as well.

In accordance with another aspect of the present invention, an insectrepellent composition is provided which comprises a compound of FormulaI, above, and a sustained release carrier.

The compounds described herein may also be used as a component ofcosmetic or personal care compositions, as well as household cleaningcompositions, in order to impart insect repellent activity to suchcompositions.

The present invention may also be embodied in articles of manufacturecomprising fabrics, e.g. mosquito netting, in which is incorporated acompound of Formula I, above.

The present invention further provides coating compositions, e.g. forarchitectural and industrial coating applications, including a compoundof Formula I above, and methods of using such compositions to preventinfestation of structural surfaces by insect pests.

As will appear in the detailed description that follows, compounds ofFormula I, above, have utility as repellents against a wide variety ofinsect pests.

In published International Application PCT/IN02/00228 mentholpropyleneglycol-carbonate and menthol ethyleneglycol-carbonate aredisclosed as ingredients of a “cooling cum moisturizing agent” for useas an optional component in an anti-itch formulation. Insofar as isknown, however, the compounds described herein as being useful for thepractice of this invention have not previously been disclosed orsuggested as having insect repellent activity.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a bar graphic of experimental data showing dose dependentinhibition of mosquito biting by application of a lotion containingvarious concentrations of racemic menthol propyleneglycol-carbonate.

FIG. 2 is a bar graph showing the repellent effect provided by mentholpropyleneglycol-carbonate against the common housefly (Musca domestica)alighting on raw beef, as a function of the concentration of mentholpropyleneglycol-carbonate applied to the beef.

FIG. 3 is a bar graph showing the superior repellent effect provided bymenthol propyleneglycol-carbonate in combination with DEET, on the onehand, and citronella, on the other hand, against mosquito bitingactivity, as compared to menthol propyleneglycol-carbonate alone, DEETabove and citronella alone. A synergistic repellent effect was obtainedwith the combination of menthol propyleneglycol-carbonate and DEET.

DETAILED DESCRIPTION OF THE INVENTION

Compounds used in the practice of this invention are available fromcommercial sources, including Symrise & Co KG and Takasago InternationalUSA, among others. The menthol carbonate derivatives may, if desired, beprepared from readily available starting materials, in the mannerdescribed in U.S. Pat. No. 5,703,123 to Pelzer, et al. and U.S. Pat. No.3,419,543 to Mold, et al.

The following definitions apply with reference to compounds encompassedby Formula I, above:

The term “alkyl” refers to straight- or branched-chain unsubstitutedalaphatic hydrocarbon groups of 1-12 carbon atoms. Similarly, the term“alkyl”, when used in combination form to name a substituent such as“hydroxyalkyloxy”, “hydroxyalkyl”, “alkylamine” or the like, refers to astraight- or branched-chain alaphatic hydrocarbon group of 1-12 carbonatoms. The expression “lower alkyl” refers to unsubstituted, straight-or branched-chain alkyl groups of 1-6 carbon atoms.

The term “substituted alkyl” refers to an alkyl group substituted by,for example, 1-25 substituents, and most preferably 1-4 substituents.Substituents may include, without limitation, hydroxy, alkoxy, halo,cycloalkoxy, oxo, amino, monoalkylamino, dialkylamino, aryl andsubstituted aryl. Among the alkyl substituents noted above, particularlypreferred are hydroxy substituents.

The term “lower alkenyl” refers to straight- or branched-chain,unsubstituted, unsaturated hydrocarbon groups of 1-6 carbon atoms.Examples of lower alkenyl groups include ethenyl, propenyl, butenyl,pentenyl and the like.

The term “substituted alkenyl” refers to an alkenyl group substitutedby, for example, 1-12 substituents, and most preferably, 1-4substituents. The substituents are the same as those described abovewith reference to the alkyl groups.

The term “aryl” refers to monocyclic or polycyclic aromatic hydrocarbongroups having 6-15 carbon atoms in the ring portion, such as phenyl,naphthyl, biphenyl, indenyl, fluorenyl or the like, each of which may besubstituted.

The term “substituted aryl” refers to an aryl group, as defined above,substituted by, for example, 1-7 substituents, and preferably, 1-4substituents, such as those described above with reference to thesubstituted alkyl and alkenyl groups.

The term “halogen” refers to fluorine, chlorine, bromine or iodine.

When a moiety is described herein as substituted with more than onesubstituent, it is intended that each of the multiple substituents bechosen independently from among the substituents mentioned above.

Compounds encompassed by Formula I, above, have asymmetric carbon atoms,and therefore, can exist as paired enantiomers, differing in theiroptical activity. The compounds may be used in enantiomerically pureform, in racemic form or in other mixed forms.

Preferred compounds for use in the practice of this invention include:menthol propyleneglycol-carbonate, isopulegol propyleneglycol-carbonate,menthyl-9-hydroxynonyl-carbonate, menthoxy-propane-1,2-diol, andN-ethyl-p-menthane-3-carboxamide.

The menthol propyleneglycol-carbonate and analogs described herein havebeen shown to be effective repellents of a wide range of insect peststhat are harmful to man, either directly as disease vectors, orindirectly as destroyers of crops, food products, or textile fabrics. Asexemplified hereinbelow, remarkable repellent effects have been achievedwith respect to flying insects, such as mosquitoes and house flies,crawling insects, such as ants and boring insects, such as termites. Thetesting carried out to date indicates that compounds of Formula I,above, will also be effective as repellents against the followinginsects: aphids, beetles, bees, borers, bugs, caspids, caterpillars,cockroaches, fleas, flea hoppers, fruit flies, grass hoppers, leafhoppers, leaf miners, mealy bugs, miners, mites, moths, scales, spiders,slugs, ticks, thrips, wasps, weevils, white flies and yellow jackets.Specific examples of insect species against which the compoundsdescribed herein may be used as repellents include the following:

Aphids:

Acyrthosiphon pisum, Aphis fabae, bean aphid, Aphis glycines, Soybeanaphid, Aphis gossypii, melon aphid, Aphis middletonii, erigeron rootaphid, Aphis nerii, oleander aphid, Aphis spiraecola, spirea aphid,Aulacorthum circumflexum, crescentmarked lily aphid, Bemisia tabaci,sweetpotato whitefly, Brachycolus heraclei, celery aphid, Brevicorynebrassicae, cabbage aphid, Cavariella aegopodii, an aphid, Cerataphisorchidearum, fringed orchid aphid, Dysaphis apiifolia, rusty-bandedaphid, Hyperomyza lactucae, an aphid, Lipaphis erysimi, turnip aphid,Macrosiphum euphorbiae, potato aphid, Macrosiphum luteum, orchid aphid,Melanaphis sacchari, sugarcane aphid, Myzus ornatus, ornate aphid, Myzuspersicae, green peach aphid, Neomyzus circumflexum, crescentmarked lilyaphid, Neotoxoptera formosana, onion aphid, Patchiella reaumuri, taroroot aphid, Pentalonia nigronervosa, banana aphid, Rhopalosiphum maidis,corn leaf aphid, Rhopalosiphum nymphaea, waterlily aphid, Rhopalosiphumrufiabdominalis, rice root aphid, Toxoptera aurantii, black citrusaphid, Toxoptera citricida, brown citrus aphid, Vesiculaphis caricis, anaphid,

Ants:

Anoplolepis longipes, longlegged ant, Pheidole megacephala, bigheadedant, Formica spp., field ants, Lasius spp., Cornfield ants, amponotusspp., carpenter ants, Pogomomyrmex spp., harvester ants, Tetramoriumcaesptium, pavement ants, Monomorium pharoanis, pharaoh ants, Solenopsismolesta, thief ants, Linepithema humile, Argentine ants, Solemopsis spp.Fire ants, Tapinoma melanocephalum, Ghost ants, Crematogaster spp.,Crematogaster ants, Paratrechina longicornis, crazy ants Anoplolepisgracilipes, yellow crazy ants,

Beetles:

Adoretus sinicus, Chinese rose beetle, Anthonomus eugenii, pepperweevil, Anthrenus sp., Carpet beetles, Apomecyna saltator, cucurbitlongicorn, Asynonychus godmani, Fuller rose beetle, Attagenus Mezatoma,Black carpet beetle, Carpophilus hemipterus, driedfruit beetle,Carpophilus humeralis, yellowshouldered souring beetle, Chaetocnemaconfinis, sweetpotato flea beetle, Coleoptera, a beetle, Cosmopolitessordidus, banana root borer, Cryptorhynchus mangiferae, mango weevil,Cylas formicarius elegantulus, sweetpotato weevil, Elytroteinussubtruncatus, Fijiian ginger weevil, Epitrix hirtipennis, tobacco fleabeetle, Euscepes postfasciatus, West Indian sweetpotato weevil, Harmoniaaxyridis, Multicolored Asian Lady Beetle, Hypothenemus obscurus,tropical nut borer, Lasioderna serricorne, Cigarette beetle, Lematrilinea, threelined potato beetle, Listroderes difficilis, vegetableweevil, Maruca testulalis, bean pod borer, Omphisa anastomosalis,sweetpotato vine borer, Orchidophilus aterrimus, orchid weevil,Orchidophilus peregrinator, lesser orchid weevil, Oryzaephilus mercator,merchant grain beetle, otiorhynchus cribricollis, cribate weevil,Popillia japonica, Japanese Beetle, Protaetia fusca, mango flowerbeetle, Stegobium paniceum, Drugstore beetle, Tribolium castaneum, redflour beetle, Tribolium confusum, confused flour beetle, Xyleborusaffinis, a scolytid beetle, Xyleborus crassiusculus, a scolytid beetle,Xyleborus fornicatus, a scolytid beetle, Xylosandrus compactus, blacktwig borer,

Bees:

Apis mellifera, Africanized or European honey bee, Xylocopa sp.,Carpenter bees,

Borers:

Maruca testulalis, bean pod borer, Ostrinia nubilalis, European cornborer,

Bugs:

Antianthe expansa, solanaceous treehopper, Coptosoma xanthogramma, blackstink bug, Cyrtopeltis modestus, tomato bug, Draeculacephala minerva,grass sharpshooter, Empoasca stevensi, Stevens leafhopper,Gnorimosphaeroma sp., pillbugs Hyalopeplus pellucidus, transparentwingedplant bug, Hemiptera, a bug, Lamenia caliginea, a fulgorid planthopper,Lepismatidae spp., Silverfish, Leptocoris trivittatus, Eastern Box bug,Leucopoecila albofasciata, a fleahopper, Melormenis basalis, West Indianflatid, Nabis capsiformis, pale damsel bug, Nezara viridula, southerngreen stink bug, Nysius nemorivagus, a lygaeid bug, Nysiusnigriscutellatus, a lygaeid bug, Plautia stali, oriental stink bug,Pycnoderes quadrimaculatus, bean caspid, Siphanta acuta, torpedo bug,Spanagonicus albofasciatus, whitemarked fleahopper, Spissistilusfestinus, threecornered alfalfa hopper, Tarophagus colocasiae, tarodelphacid, Vanduzeea segmentata, Van Duzee treehopper,

Caspids:

Pycnoderes quadrimaculatus, bean caspid,

Caterpillars:

Achaea janata, croton caterpillar, Acrolepia assectella, leek moth,Agrius cingulatas, sweetpotato hornworm, Agrotis ipsilon, black cutworm,Amorbia emigratella, Mexican leafroller, Anacamptodes fragilaria, koahaole looper, Anua indiscriminata, guava moth, Cadra cautella, almondmoth, Chrysodeixis eriosoma, green garden looper, Conoderus amplicollis,Gulf wireworm, Cryptoblabes gnidiella, Christmas berry webworm,Cryptophlebia illepida, koa seedworm, Cryptophlebia ombrodelta, litchifruit moth, Daphnis nerii, oleander hawk moth, Delia platura, seedcornmaggot, Empoasca solana, southern garden leafhopper, Hedyleptablackburni, coconut leafroller, Helicoverpa zea, corn earworm, Hellulaundalis, imported cabbage webworm, Keiferia lycopersicella, tomatopinworm, Lampides boeticus, bean butterfly, Othreis fullonia, Pacificfruit-piercing moth, Pelopidas thrax, banana skipper, Penicellariajocosatrix, mango shoot caterpillar, Peridroma saucia, variegatedcutworm, Phthorimaea operculella, potato tuberworm, Pieris rapae,imported cabbageworm, Plutella xylostella, diamondback moth, Spodopteraexempta, nutgrass armyworm, Spodoptera exigua, beet armyworm, Spoladearecurvalis, Hawaiian beet webworm, Strymon echion, larger lantanabutterfly, Trichoplusia ni, cabbage looper, Vanessa cardul, painted ladybutterfly,

Cockroaches:

Blaberus craniifer, deaths-head cockroach, Blaberus discoidalis, discoidcockroach, Blatta orientalis, oriental cockroach, Byrsotria fumigata,Cuban burrowing cockroach, Diploptera punctata, beetle roach, Eublaberusposticus, Cave dwelling cockroach, Gromphadorhina portentosa, hissingcockroach, Leucophaea maderae, Madeira cockroach, Periplaneta americana,common American cockroach, Periplaneta brunea, brown cockroach,Periplaneta fulginosa, dusky brown cockroach, Schultesialampyridiformis, firefly roach, Supella longipalpa, brown bandedcockroach,

Fleas:

Ctenocephalides felis (Bouche), cat flea, Siphonaptera, a flea,

Fleahoppers:

Leucopoecila albofasciata, a fleahopper, Spanagonicus albofasciatus,whitemarked fleahopper,

Plies:

Asilidae sp., robber flies, Bactrocera cucurbitae, melon fly,Ceratopogonidae sp., Chironomidae sp., Conoderus amplicollis, Gulfwireworm, Contarinia maculipennis, blossom midge, Culicidae sp.Dasineura mangiferae, mango blossom midge, Delia echinata, carnation tipmaggot, Delia platura, seedcorn maggot, Eumerus figurans, ginger maggot,Eurychoromyiidae sp. Broad headed flies, Milichiidae sp. Small flies,Mydidae sp. True flies, Musca domestica, house fly, Ophiomyia phaseoli,bean fly, Phoridae sp., Sciaridae sp., Simuliidae sp. Black flies,Syrphidae sp. Flower flies, Tachinidae sp. Parasitic flies, Tanyderidaesp. Primitive crane flies, Therevidae sp. Stiletto flies,

Fruitflies:

Bactrocera cucurbitae, melon fly, Bactrocera dorsalis, oriental fruitfly, Bactrocera latifrons, solanaceous fruit fly, Ceratitis capitata,Mediterranean fruit fly, Drosophilidae sp. Fruit fly, Tephritidae sp.Fruit flies,

Grasshoppers:

Atractomorpha sinensis, pinkwinged grasshopper, Conocephalus saltator,longhorned grasshopper, Elimaea punctifera, narrowwinged katydid,

Leafhoppers:

Empoasca solana, southern garden leafhopper, Empoasca stevensi, Stevensleafhopper, Sophonia rufofascia, two-spotted leafhopper,

Leafminers:

Acrolepiopsis sapporensis, Asiatic onion leafminer, Bedellia orchilella,sweetpotato leafminer, Liriomyza brassicae, serpentine leafminer,Liriomyza huidobrensis, pea leafminer, Liriomyza sativae, vegetableleafminer, Liriomyza trifolii, chrysanthemum leafminer, Pjyllocinistiscitrella, Citrus Leafminer

Mealybugs:

Antonina graminis, Rhodesgrass mealybug, Dysmicoccus brevipes, pineapplemealybug, Dysmicoccus neobrevipes, gray pineapple mealybug, Ferrisiavirgata, striped mealybug, Geococcus coffeae, coffee root mealybug,Nipaecoccus nipae, coconut mealybug, Nipaecoccus viridis, hibiscusmealybug, Phenacoccus gossypii, Mexican mealybug, Planococcus citri,citrus mealybug, Pseudococcus dendrobiorum, dendrobium mealybug,Pseudococcus jackbeardsleyi, Jack Beardsley mealybug, Pseudococcuslongispinus, longtailed mealybug, Pseudococcus virburni, obscuremealybug,

Miners:

Melanagromyza splendida, safflower stemminer,

Mites:

Aculops lycopersici, tomato russet mite, Brevipalpus obovatus, privetmite, Brevipalpus phoenicis, red and black flat mite, Calacarusbrionesae, papaya leaf edgeroller, Eotetranychus sexmaculatus,sixspotted mite, Eriophyes mangiferae, mango bud mite, Eutetranychusbanksi, Texas citrus mite, Oligonychus mangiferus, mango spider mite,Panonychus citri, citrus red mite, Polyphagotarsonemus latus, broadmite, Siteroptes framinum, grass mite, Steneotarsonemus furcatus, tarotarsonemid mite, Steneotarsonemus pallidus, cyclamen mite, Tetranychuscinnabarinus, carmine spider mite, Tetranychus desertorum, desert spidermite, Tetranychus neocalidonicus, vegetable mite, Tetranychus tumidus,tumid spider mite, Tuckerella ornata, Tuckerellid mite, Tuckerellapavoniformis, Tuckerellid mite, Varroa jacobsoni, Varroa mite,

Moths:

Actias luna, Luna moth, Anisota sp., Oakworm moths, Antheraeapolyphemus, Polyphemus moth, Automeris io, Io moth, Callosamia sp., silkmoth, Eacles imperialis, Imperial moth, Hemileuca maia, easternbuckmoth, Hyalophora cecropia, silk moth, Plodia interpunctella, IndianMeal Moth, Plutella xylostella, Diamondback moth, Sphingicampa sp.,Honey locust moths, Tineola bisselliella, clothing moth, Trichophagatapetzella, carpet or tapestry moth,

Mosquitoes:

Aedes sp, Anopheles sp., Coquilltettidia sp., Culex sp., Culiseta sp.,Ochlerotatus sp., Psorophora sp.,

Scales:

Abgrallaspis cyanophylli, an armored scale, Aspidiella hartii, aturmeric root scale, Aspidiotus destructor, coconut scale, Aspidiotusnerii, oleander scale, Asterolecanium pustulans, oleander pit scale,Ceroplastes rubens, red wax scale, Chrysomphalus aonidum, Florida redscale, Chrysomphalus dictyospermi, dictyospermum scale, Clavaspisherculeana, an armored scale, Coccus hesperidum, brown soft scale,Coccus longulus, long brown scale, Coccus viridis, green scale, Diaspisboisduvalii, Boisduval scale, Diaspis bromeliae, pineapple scale,Duplaspidiotus claviger, an armored scale, Fiorinia fioriniae, avocadoscale, Furcaspis biformis, red orchid scale, Hemiberlesia lataniae,latania scale, Hemiberlesia rapax, Greedy scale, Howardia biclavis,mining scale, Icerya purchasi, cottony-cushion scale, Ischnaspislongirostris, black thread scale, Kilifia acuminata, acuminate scale,Melanaspis bromeliae, brown pineapple scale, Morganella conspicua, anarmored scale, Parasaissetia nigra, nigra scale, Parlatoria proteus,variable chaff scale, Pinnaspis aspidistrae, fern scale, Pinnaspis buxi,ti scale, Pinnaspis strachani, Hibiscus snow scale, Protopulvinariamangiferae, mango soft scale, Pseudaulacaspis cockerelli, Cockerellscale, Pulvinaria mammeae, large cottony scale, Pulvinaria psidii, greenshield scale, Pulvinaria urbicola, cottony sweetpotato scale, Saissetiacoffeae, hemispherical scale, Saissetia neglecta, Caribbean black scale,Vinsonia stellifera, stellate scale,

Spiders:

Araneidae sp., Orb web spiders, Atrax sp., Funnel web spiders,Loxosceles sp., Recluse spiders, or violin spiders, Lycosidae sp., Wolfspiders, Pholcidae sp., Cellar spiders, Salticidae sp., Jumping spiders,Tegenaria agrestis, Hobo or Aggressive house spiders,

Slugs:

Vaginulus plebius, brown slug, Veronicella leydigi, black slug,

Ticks:

Amblyomma americanum, Lone Star Tick, Dermacentor variabilis, AmericanDog Tick, Ixodes scapularis, Deer Tick, Rhipicephalus sanguineus, Browndog tick,

Thrips:

Chaetanaphothrips orchidii, anthurium thrips, Chaetanaphothripssignipennis, banana rust thrips, Dichromothrips corbetti, vanda thrips,Echinothrips americanus, a thrips, Elixothrips brevisetis, banana rindthrips, Frankliniella occidentalis, western flower thrips, Frankliniellashultzei, yellow flower thrips, Haplothrips gowdeyi, black flowerthrips, Helionothrips errans, cymbidium thrips, Heliothripshaemorrhoidalis, greenhouse thrips, Hercinothrips feinoralis, bandedgreenhouse thrips, Leucothrips pierci, a thrips, Schultzei, yellowflower thrips, Sciothrips cardamomi, cardamom thrips, Scirtothripsdorsalis, a thrips, Selenothrips rubrocinctus, redbanded thrips, Thripsalliorum, a thrips, Thrips hawaiiensis, Hawaiian flower thrips, Thripsnigropilosus, chrysanthemum thrips, Thrips palmi, melon thrips, Thripstabaci, onion thrips,

Wasps:

Bephratelloides cubensis, Annona seed wasp, Eurytoma orchidearum,orchidfly, Polistes sp., Paper wasps, Sphecidae sp., Mud Dauber wasps,

Weevils:

Anthonomus eugenii, pepper weevil, Diaprepes abbreviatus, Citrus rootweevil,

Whiteflies:

Aleurocanthus spiniferus, orange spiny whitefly, Aleurodicus dispersus,spiraling whitefly, Aleurothrix antidesmae, a white fly, Aleurothrixusfloccosus, woolly whitefly, Aleurotulus anthuricola, anthurium whitefly,Bemisia argentifolii, silverleaf whitefly, Bemisia tabaci, sweetpotatowhitefly, Crenidorsum sp., a whitefly, Orchamoplatus mammaeferus, crotonwhitefly, Paraleyrodes perseae, plumeria whitefly, Trialeurodesvaporariorum, greenhouse whitefly,

Yellowjackets:

Vespula vulgaris, common yellowjacket, Vespula maculifrons, easternyellowjacket, Vespula germanica, german yellowjacket, Vespa crabro,giant hornet

In carrying out the methods of the invention, the compounds of Formula Imay be used neat, or as a component of a composition obtained byadmixture with a suitable carrier or vehicle. The nature of the carrieror vehicle will vary depending on the mode of application oradministration.

The insect repellent compositions of the invention are formulated toinclude an effective amount of a compound of Formula I which isgenerally from about 1 to about 80 wt %, based on the total weight ofthe composition. It has been found that compositions in which a compoundof Formula I is present in an amount of less than 1 wt % does notproduce the intended effect. The composition may optionally include fromabout 3 to about 80 wt % of a skin conditioner, with the balance beingone or more inactive ingredients that constitute the carrier or vehicle.Particularly satisfactory insect repellent effects have been obtainedusing formulations containing from about 1 to about 30 wt % of acompound of Formula I above, preferably a racemic mixture of mentholpropyieneglycol-carbonate. Isopulegol propyleneglyol-carbonate alsoproduced good results. These compounds can be safely applied to theintegument or skin of humans, livestock, pets, plants, plant parts andseeds.

The insect repellent effect produced by the compounds described hereinmay also be incorporated in various cosmetics or personal care products,including, without limitation, perfumes, colognes, deodorants,anti-perspirants, skin creams, soaps, shampoos, hair conditioners, hairrinses, bath oils, talcs, sunblocks, sunscreens and the like; or inhousehold cleaning products including, without limitation, cleansers,detergents, fabric softeners, air fresheners, upholstery or rugshampoos, furniture polishes, floor waxes or the like, which productsmay be in either liquid or solid form. These products will typicallycontain from about 1 to about 80 wt % of a compound or mixture ofcompounds of Formula I above, based on the tare weight of the product.The insect repellent compounds may also be mixed with fertilizer, mulchand potting preparations.

The compounds of Formula I can be used as the sole insect repellent in acomposition or may be used in combination with other natural orsynthetic agents that are effective insect repellents. These include,without limitation, N,N-diethyl-m-toluamide(DEET); N,N-diethylbenzamide;citronella; Tolu balsam; Peru balsam; eucalyptus oil; Huon pine oil;camphor; cypress oil; galbanum; diethylphthalate; dimethylphathalate;dibutylphthalate;1,2,3a,4,5,5a,6,7,8,9,9a,9b-dodecahydro-3a,6,9a-tetramethylnaphtho[2,1-b]furan;4-(tricyclo[5.2.1.0^(2,6)]decylidene-8)butanal;1-ethoxy-1(2′-phenylethoxy)ethane; acetyl cedrene and propylidenephthalide.

Various auxiliary ingredients may be added to the above-describedcompositions to impart desired properties or characteristics thereto orto facilitate application or administration in a particular way. Theseauxiliary ingredients may include, without limitation, fragrances,surfactants, propellants, emulsifiers, dispersants, buffers,preservatives, antioxidants, diluents, solvents and fixatives, as iscommon practice in the art.

The deleterious activity of microorganisms may be inhibited by theinclusion of various antibacterial and antifungal agents, e.g., paraben,chlorobutanol, phenol, sorbic acid and the like.

The compositions described above may be prepared in various formsdepending on the mode of application or administration. Thus,compositions may be in the form of a lotion, cream, ointment, gel orpowder for topical application or a solution or suspension for use as anatomized or aerosol spray.

The compounds and compositions described herein may be formulated withsustained or controlled release components or carriers of various types,e.g. organic or inorganic particulates, or in alcohol or water-basedformulations for topical use, as is well known in the art.

Compositions used in practicing the invention can be prepared by variousmethods well known in the art. Typically, such compositions are preparedby intimately mixing a compound of Formula I with a suitable carriermaterial and optionally one or more auxiliary ingredients, as desired,and putting the resulting mixture into a suitable container ordispenser.

The compounds and compositions described herein are beneficially appliedto animals and plants, as well as inanimate objects to produce thedesired insect repellent effect. In most cases, the insect repellentcomposition of the invention will be topically or externally applied tothe site or surface to be treated, and the application will beperiodically repeated to maintain the desired level of insect repellent.

The compounds described herein may also be used beneficially in variouscoating compositions, such as architectural and industrial coatingproducts, in order to inhibit insect infestation by repelling insectsfrom the treated surfaces. Such coating compositions are convenientlyformulated by mixing one or more of the compounds of Formula I, above,with a conventional paint vehicle, including a suitable film-former,which is readily applied and adheres to the site or surface that is tobe protected against insect infestation. The coating composition may beapplied in various ways, including, for example, brushing, spraying ordipping.

The specific film-former to be selected for a particular applicationwill vary depending on the material and construction of the article tobe protected. After a surface is provided with a protective coating inaccordance with this invention, the active ingredient of Formula I whichis present in the coating composition provides its insect repellenteffect, thereby protecting the treated surface against infestation. Avariety of synthetic polymers are known to be useful film-formers forcoating applications. Examples of suitable polymer resins includepolyester (e.g. alkyd) resins, unsaturated polymer (e.g. acrylic)resins, vinyl ester, vinyl acetate and vinyl chloride-based resins,urethane-based resins, epoxy resins and silicone resins or combinationsthereof. Unsaturated polyester resins are formed from unsaturated acidsand anhydrides, saturated acids and anhydrides (to control the amount ofunsaturation in the final resin) and polyhydroxy alcohols, usuallyglycols. Preferred film former components are polyurethane, epoxy, alkydand silicone resins. Commercial paint vehicles which are suitable forthe practice of this invention include the following: Benwood InteriorWood Finishing penetrating stain 234 and Benwood Interior Wood Finishingpolyurethane stain 228 (both from Benjamin Moore Paints); Van SickleExterior latex paints (Van Sickle Paints, Lincoln, Nebr.); Polane G Pluspolyurethane enamel and ACRI-PRO 100 flat exterior acrylic paint (bothfrom Porter Paints, Louisville, Ky.); and Wearlon non-stick coatings(water based silicone/epoxy coatings) (Environmental Coatings, LLC).

The coating composition of the invention may include components inaddition to a compound or compounds of Formula I above, and a filmformer component, so as to confer one or more desirable properties, suchas color, hardness, strength, rigidity, permeability, water resistanceor the like. The selection of a particular component or group ofcomponents to impart such properties are within the capabilities ofthose having ordinary skill in the art.

The percentage of the repellent compound in the coating compositionrequired for effective protection against insect infestation may varydepending on the compound itself, the chemical nature of the filmformer, as well as other additives present in the composition that mayinfluence the effectiveness of the repellent compound. Generally, therepellent compound comprises between about 1 and about 80% of thecoating composition by weight, and preferably between about 5 and about50% by weight of the composition.

The compounds of Formula I, above, may be included in a paintformulation during the paint manufacturing process, or added to thepaint at the time of use. The compounds of Formula I may be simply mixedinto the paint vehicle. The repellent compound may also be covalentlybound to the polymer resin. Furthermore, the compounds of Formula I maybe incorporated with time-release materials, which provide sustainedrelease of the compounds from the coating matrix, thereby prolonging theeffectiveness of the coating and reducing the amount of active compoundnecessary to produce the insect repellent effect. Encapsulation intosuch time-release materials also protects the active ingredient from theharsh chemical environment of the coating, and tends to reducedegradation of the active compounds while trapped in the resin if theyare susceptible to degradation. Examples of suitable controlled releasematerials include: liposomes, nanocapsules, lipid microtubules, metalmicro-tubules, polymers and halloysite microtubules.

Insect repellent effects on coated surfaces are obtainable usingcompounds of Formula I, above, at a surface concentration of from about1 to about 600 mg/cm², more preferably from about 10 to about 80 mg/cm²,and most preferably from about 30 to about 50 mg/cm². Relatively higherconcentrations, on the order of from about 300 to about 600 mg/cm² willbe used to repel mosquitoes

Also within the scope of this invention is any structure or articlehaving a surface coating with a coating composed of at least onecompound of Formula I, above. The coated structure or article cancomprise any material which insect pests are likely to attack, such aslive trees, agricultural plants, ornamental plants, seeds, wood orlumber, furniture, flooring and walls.

The compounds described herein may also be incorporated into a fabricsubstrate to render the fabric insect repellent. The repellentcompound(s) may be combined with various synthetic fibers during thefiber manufacturing process, e.g. by dry spinning. Fibers which may bemade in this manner include, without limitation, polyester, polyamide(preferably nylon), acrylics and polyolefins (preferably polyethylene)fibers. The fibers or filaments thus obtained are spun into yarn whichis then woven or knitted into the finished insect repellent fabric. Ofcourse, knitted fabric may also be made from single filaments. Theresulting fiber may also be used to produce non-woven fabrics.

The repellent compound(s) may also be associated with finely dividedcarriers, having particle sizes in the micrometer to nanometer range,for inclusion in the cladding or core of spun fibers. The particularcarrier can be appropriately selected to protect the repellent compoundfrom adverse thermal effects, e.g. in melt spinning procedures. Suitableparticulate carriers for this purpose include, without limitation,polymeric capsules, halloysite microtubules and metal microtubules.Carriers such as halloysite microtubules also enable controlled releaseof the insect repellent from the resultant fibers. See also U.S. Pat.No. 6,326,015, which relates to slow-release insect repellent fabric.

Alternatively, the insect repellent may be applied to the finishedfabric, e.g. by spraying, impregnation, padding (by means of animmersion tank and squeeze roller) or the like.

The insect repellent fabric can be converted into a wide variety ofuseful articles including, without limitation, garments such as BattleDress Uniforms used by the military, tent fabric, mosquito netting,bandannas, animal bedding materials or protective wraps for trees andother plants. The insect repellent compound(s) may also be applied tothe fabric after it is made into a finished article. Cotton cloth ornetting may also be rendered insect repellent in accordance with thisinvention.

The insect repellent compounds described herein are preferably used forrendering mosquito netting insect repellent. A practical procedure fortreating mosquito netting with insecticide is described atwww.pathcanada.org, the details of which are incorporated by referenceherein.

Barrier sheets effective for protecting wooden structures from termitesand other boreing insects may also include one or more insect repellentcompounds of Formula I, above. Such barrier sheets may be prepared inthe form of polymer films, which may be manufactured by conventionmolding, casting or extruding methods, depending on the nature of thepolymer used. Incorporation of the insect repellent compound(s) into thepolymer film may be carried out in a manner similar to that describedabove for synthetic polymer fibers, including controlled-releaseembodiments. The insect repellent may also be applied to a filmsubstrate by means of a physical melt-bonded mixture of compatiblepolymer and repellent, which is bonded in spaced apart spots to the filmsubstrate, in the manner described in U.S. Pat. No. 6,319,511.

Insect repellent-containing fibers, prepared as described above, mayalso be used to form a protective barrier for control of agriculturalpests, as described in U.S. Pat. No. 6,052,943.

The following examples set forth further details regarding theinvention. These examples are provided for illustrative purposes only,and are not intended to limit the invention in any way. These examplesshow the results of tests conducted to determine the efficacy of certaincompounds of Formula I, above, as insect repellents.

Examples 1 through 9 show the insect repellent effect of compounds ofFormula I, above.

EXAMPLE 1

Adult mosquitoes (Culex quinquefasciatus) were kept inside a screenedchamber measuring 2 ft×2 ft×2 ft at a density of 200 mosquitoes perchamber. The mosquitoes are aged 3 to 10 days after emergence fromlarvae and were starved for 24 hours prior to each test. Each of thetest compounds (supplied as a gift from Symrise GmbH & Co Kg,Holzminden, Germany) was added to a commercial lotion base (CrestoLaboratories, Manila, Philippines) and thoroughly mixed into the lotionusing an electronic mixer. The resulting formulation was applied fromthe elbow to the tip of the fingers of human volunteers. The coated armsof the volunteers were then inserted, in turn, inside the chamber up tothe elbow. The protection time was determined for each formulation asthe length of time until a mosquito had taken its first bite, afterwhich the test was terminated. The data in Table 1 show the protectiontime determined in this manner for the compounds tested. TABLE IProtection Time Chemical Name (Synonym) (minutes)*1-5-methyl-2-isopropyl cyclohexanol (1-menthol) 30 ± 9 5-methyl-2-(1-methylethenyl) 56 ± 7  cyclohexanol ((−)-isopulegol)menthoxy-propane-1,2-diol 68 ± 17 N-Ethyl-p-menthane-3-carboxyamide 92 ±31 menthol propyleneglycol-carbonate 68 ± 15 racemic mentholpropyleneglycol-carbonate 283 ± 17  isopulegol propyleneglycol-carbonate152 ± 36  menthyl-9-hydroxynonyl-carbonate 79 ± 14*Mean ± Standard error of the mean for 4 volunteers per test group.Compounds were added to the lotion base at a concentration of 5 wt %,based on the total weight of the composition.

The data show that the racemic form of menthol propyleneglycol-carbonateis almost nine times more effective than menthol or isopulegol inpreventing mosquito bites. The performance of mentholpropyleneglycol-carbonate will vary depending upon the cosmeticformulation used for the tests.

Further experiments demonstrated that the inhibitory effect of racemicmenthol propyleneglycol-carbonate on mosquito bite occurs in a dosedependent manner. The results of these experiments are shown in FIG. 1.

EXAMPLE 2

The red ant (pharaoh ant, Monomorium pharaonis) was selected for thisant repellent test since it has a worldwide distribution and is known tobe a household pest.

Red ants are attracted to the smell of food. The attractant in thisexperiment was a piece of chocolate, which was placed on a tabletop 5hours before the test. Within 2 hours after being released on the groundaround the table, the red ants established a route from the ground upthe table legs. At the 5th hour, a filter paper impregnated with racemicmenthol propyleneglycol-carbonate at two concentrations was placedaround the middle portion of the table leg. The test compound wasdissolved in ethanol and impregnated into a pre-weighed, 2 inch by 7inch piece of filter paper. After complete evaporation of ethanol, thefilter paper was weighed and the final weight of the test compound wasdetermined per cm² of the filter paper. The control employed was thesame filter paper soaked with ethanol only. The time for the first antto cross the filter paper barrier was determined.

The data are shown in Table II. The results show that racemic mentholpropyleneglycol-carbonate, at appropriate concentration, is an effectiverepellent against red ants. TABLE II Concentration Time to crossbarrier * TEST GROUP (mg/cm²) (Minutes) CONTROL 0 <1 Racemic menthol 1563 ± 18 propyleneglycol-carbonate Racemic Menthol 30 760 ± 76 propyleneglycol-carbonateEach data point is the mean ± SEM of 5 tests.

EXAMPLE 3

Common houseflies, Musca domestica, were collected using butterfly netsand placed inside a net cage measuring 1 cubic foot. The houseflies wereacclimatized in the new environment for 3 hours prior to the test. Astandard slice of raw beef was placed in the middle of the cage toattract the houseflies. Racemic menthol propylene glycol-carbonate wasadded to 95% ethanol at concentrations ranging from 10% to 50% v/v.These experimental solutions were uniformly sprayed with a spray bottleon the surface of the beef. Control tests utilized the 95% ethanolsolution without any of the test compound and sprayed on the surface ofthe beef in the same manner. Protection time refers to the time at whichthe first housefly landed on the surface of the raw beef.

The data obtained during the above-described tests appears in FIG. 2,which shows a dose-related inhibition of housefly landing on the surfaceof the raw beef, indicating that menthol propylene glycol carbonate waseffective in protecting treated surfaces against housefly infestation.

EXAMPLE 4

Effect of Combining Menthol Propyleneglycol-Carbonate with DEET andCitronella

To test the effectiveness of menthol propyleneglycol-carbonate(mentholpropyleneglycol-carbonate) in enhancing the effect of the known insectrepellent DEET against mosquito biting activity, this study wasundertaken by combining racemic menthol propyleneglycol-carbonate withDEET (purchased from Sigma-Aldrich). The two chemicals were added at 10%w/w in an Hydrophilic ointment base (E. Fougera & Co., Melville, N.Y.)and applied on the exposed arms of human volunteers. The treated armswere inserted inside a mosquito chamber and the protection time wasdetermined. The data obtained during this study appears in FIG. 3, whichshows that the addition of 10% racemic menthol propyleneglycol carbonatein an ointment base with DEET resulted in a greater protection time, ascompared with either of the two active compounds alone. The recordeddata represents the mean and standard error of 3 human volunteers.

To test the effectiveness of menthol propyleneglycol-carbonate inenhancing the effect of another known mosquito repellent product, anexperiment was undertaken in Which menthol propyleneglycol-carbonate wasadded at a concentration of 10% w/w to a citronella-based product(Natrapel) manufactured by Tender Corporation (Littleton, N.H.).Citronella oil is a malodorous natural extract from the leaves of theplant, Cymbopogon nardus, with insect repellent activity. mentholpropyleneglycol-carbonate increased the protection time of Natrapel from23 minutes to 108 minutes, thereby demonstrating that this chemical canbe used to augment the effect of weaker acting formulated products, suchas those containing citronella oil.

EXAMPLE 5

Outdoor Mosquito Tests

To validate the efficacy of menthol propyleneglycol-carbonate underambient conditions in nature, this chemical was mixed in an ointmentbase at 10% w/w and applied to the exposed arms of human volunteers whoremained outdoors during the peak period of mosquito biting, beginningat 3:00 PM. The protection time was recorded and compared with thatobtained from human volunteers using a commercially available insectrepellent (OFF! Skintastic; 7% DEET) manufactured by SC Johnson & Sons,Inc. (Racine, Wis.). Control ointment consisted of Fougera ointmentwithout any active ingredient. The protection time was determined for 3human volunteers for each test group.

Table III below shows that the efficacy of 10% racemic mentholpropyleneglycol-carbonate is somewhat better than that of OFF!Skintastic, thereby demonstrating that the effects seen in thelaboratory can be duplicated under natural conditions. TABLE IIIPROTECTION TIME STUDY GROUP (minutes ± SEM) CONTROL 10 ± 3 OFF!SKINTASTIC 194 ± 4  10% Racemic menthol propyleneglycol carbonate 227 ±19

EXAMPLE 6

Inhibition of Termite Infestation

The milk termite, Coptotermes vastator, is a pest found in tropical andsub-tropical areas. To test the efficacy of racemic mentholpropyleneglycol-carbonate, this chemical was dissolved in 95% ethanol atconcentration of 10% w/w and pieces of pre-weighed soft wood wereimmersed in the solution for 24 hours. After impregnation, the wood wasallowed to dry in air to remove the ethanol which has a lower flashpoint. The dry wood was reweighed to determine the total amount ofracemic menthol propyleneglycol-carbonate absorbed into the wood. Theweight of racemic menthol propyleneglycol-carbonate absorbed was 26milligrams per gram of wood. Controls were prepared using woodimpregnated with 95% ethanol alone.

The wood test samples were placed on top of a fallen jackfruit tree(Artocarpus heterophylla) heavily infested by termites under ambient,natural, outdoor conditions for a period of 2 months. At the end of thetest period, the wood samples were cleaned of debris and termites, driedin the sun and weighed. The degree of wood preservation was determinedby the amount of weight loss during the test period. TABLE IV TreatmentGroup Percent of weight loss CONTROL 26.6 ± 7.1 Racemic mentholpropyleneglycol carbonate  0.8 ± 0.4

The data in Table IV show that termites were able to destroy the wood inthe control group within the period of the study. When periodicallychecked visually, termites were seen within the wood samples in thecontrol group. However, when racemic menthol propyleneglycol-carbonatewas impregnated into the wood, the termites were completely preventedfrom consuming the wood, as evidenced by the minimal weight loss of theexperimental wood samples.

EXAMPLE 7

Effect of Menthol Propyleneglycol-Carbonate Against Fire Ants

Fire ants are bothersome pests in the southern United States. Thetropical fire ant (Solenopsis geminata Fabricius) is native to theUnited States. However, the more aggressive imported species of the redants (S. invicta) is dominating the southern part of the United Statesbecause of its aggressiveness. Fire ants are known to damage 57 speciesof cultivated plants. They feed on germinating seeds as well as otherinsects. Because of attraction to electrical currents, they also causeconsiderable damage to heat pumps, air conditioning, telephone junctionboxes, transformers and traffic lights. Fire ants are notorious fortheir stinging behavior and cause localized intense burning and scarringin humans.

In this study, the repellent effect of racemic mentholpropyleneglycol-carbonate was examined by preparing a solution of thischemical in ethanol at concentration of 50% (v/v). The solution wassprayed with a pump spray dispenser (Arminak & Associates, Duarte,Calif.) to a bait composed of sugary food (in this case, peanut butter).The control was composed of ethanol alone. This study was conducted inFort Pierce, Fla. The protection time was measured as the time when thefirst ant started consuming the bait. The data in Table V show that baitsprayed with racemic menthol propyleneglycol-carbonate solution wasprotected from fire ants for at least 5 hours. The experiment wasterminated after 5 hours of observation. Each study group was composedof 4 replicates. In the control which was sprayed with ethanol alone,the fire ants (s. invicta) were seen on the bait within 3 minutes afterthe spray was applied. TABLE V PROTECTION TIME Spray with ethanol alone(Control) 3 minutes Spray with 50% Racemic menthol >5 hourspropyleneglycol-carbonateEffect of Entrapped Menthol Propyleneglycol Carbonate in Halloysite Clayin Repelling Mosquitoes.

This study was conducted to evaluate the suitability of encapsulation orentrapment as a means of reducing the amount of racemic mentholpropyleneglycol-carbonate required to produce a repellent effect and toprovide a means of protecting the active material from degradation byother excipients in the formulation or from high temperatures associatedwith manufacturing, as in the case of impregnation of textile materials.The halloysite clay represents an example of many other suitableencapsulation materials available in the industry and is not intended asa limitation of the scope of this invention.

Halloysite clay is a naturally derived, nontoxic, biodegradable materialtypically used in the manufacture of porcelain, bone china and finechina. U.S. Pat. No. 5,651,976 to Price and Gaber describes a new methodof controlled release using microtubules made from halloysite clay.These microtubules are characterized as a cylinder with a hallow core ofapproximately 0.2 micrometers, which can be filled with an activecompound, enabling slow release of active ingredients from the hollowcore. The halloysite entrapped racemic menthol propyleneglycol-carbonateused in this study was supplied as a gift from Federal Technology Group(Bozeman, Mont.), with a total entrapped active material determined at17% of the total weight. The control consisted of halloysite claywithout the entrapped racemic menthol propyleneglycol-carbonate.Cosmetic formulation used in this study was an aloe vera moisturizingcream (General Nutrition Corp., Pittsburgh, Pa.). The halloysiteentrapped racemic menthol propyleneglycol-carbonate was added to themoisturizing cream at a total concentration of 20% w/w, with the totalactive material in the formulation at 3.4%. In the halloysite control,halloysite without racemic menthol propyleneglycol-carbonate was addedto the moisturizing cream at 20% w/w. A reference formulation wasincluded which was composed of 20% w/w of racemic mentholpropyleneglycol-carbonate in aloe vera cream, with aloe vera cream usedas a control. These formulations were tested on human volunteers in thestandard mosquito chamber test in which the formulation was applied onthe forearm and inserted inside the chamber. Protection time wasmeasured as the time at which the human subject experienced the firstmosquito bite. Each study comprised three human volunteers.

The data recorded in Table VI show that incorporation of racemic mentholpropyleneglycol-carbonate in halloysite clay reduced the totalrequirement for this active material, but produced essentially the samerepellent effect. The protection time for the 20% racemic mentholpropyleneglycol-carbonate cream was similar to that observed in 3.4%menthol propyleneglycol-carbonate entrapped in halloysite clay. TABLE VIPROTECTION TIME (Mean ± SEM) Control aloe vera cream 17 ± 4 20% racemicmenthol propyleneglycol- 93 ± 6 carbonate in aloe vera cream Controlhalloysite cream 30 ± 3 3.4% menthol propyleneglycol-carbonate 95 ± 9entrapped in halloysite

EXAMPLE 9

Effect of Racemic Menthol Propyleneglycol-Carbonate on Stable Flies

The stable fly or dog fly (Stomoxys calcitrans) is similar in size tohouseflies and probably the most problematic insect pest in dairy cattleand other agricultural animals. Because of the popularity of horsebreeding, these flies are now also a major problem in horse stables aswell. Stable flies feed by piercing the skin and sucking the blood,causing pain and annoyance to farm animals. Stable fly infestationcauses weight loss in cattle by as much as 25% and decrease in milkproduction by as much as 60%. In the absence of animals, stable flieswill also attack humans.

To test the effectiveness of racemic menthol propylene glycol carbonate,a 50% solution was prepared in 95% ethanol and sprayed using a standardspray bottle. Stable flies were collected by placing a screened cagecontaining (Peaceful Valley Farm Supply, Grass Valley, Calif.) baitbeside a horse stable one day prior to the test. Approximately 200stable flies were collected from each cage. The test bait comprisingpieces of beef was placed in an aluminum pan at the bottom of thecollecting cage. The test was conducted using meat sprayed with 50%racemic menthol propyleneglycol-carbonate solution, with a controlcomposed of meat sprayed with ethanol alone. The test was conducted induplicate. The number of stable flies landing and feeding on the meatwas counted periodically.

The data in Table VII below show that racemic mentholpropyleneglycol-carbonate was effective in preventing stable flies fromfeeding on the treated meat. Although one or two flies landed on thetreated meat, these flies did not linger to feed but moved onimmediately. In the control group, the flies landed immediately andincreased in numbers. The racemic menthol propyleneglycol-carbonatespray remained very effective for at least 5 hours and lost its efficacyby nine (9) hours from the initial single application. TABLE VII Effectof menthol propyleneglycol-carbonate spray on stable flies. Number offlies landing on the bait TIME (minutes) CONTROL EXPERIMENTAL 1  3 0 5 8 0 30  15 0 60  >30* 0 120 >30 0 180 >30 1 240 >30 1 300  12 0 540 >30>30*The bait was extensively covered with flies and could not be countedaccurately.

The data set forth in the foregoing examples indicate that compounds ofFormula I, above, are effective as insect repellents.

A number of patent documents are cited in the foregoing specification inorder to aid in describing the sate of the art to which this inventionpertains. The entire disclosure of each of these citations isincorporated by reference herein.

While certain embodiments of the present invention have been describedand/or exemplified above, various other embodiments will be apparent tothose skilled in the art from the foregoing disclosure. The presentinvention is, therefore, not limited to the particular embodimentsdescribed and/or exemplified, but is capable of considerable variationand modification without departure from the scope of the appendedclaims.

1. A method for repelling insects from a site which comprises applyingto said site an insect repelling amount of a compound of the formula:

wherein R represents a straight or branched chain, substituted orunsubstituted lower alkyl radical, or a straight or branched chain,substituted or unsubstituted lower alkenyl radical; X represents acarbonyl linking group (—C(═O)—) or a valence bond; n is 0 or 1; and R′represents a radical selected from the group consisting of substitutedor unsubstituted hydroxyalkyloxy and substituted or unsubstitutedhydroxyalkyl, when n is 1; and R′ represents an alkylamine radical whenn is
 0. 2. The method of claim 1 wherein the compound of Formula I isapplied in the form of a composition, also including a suitable carrier,the amount of said compound being from about 1 wt % to about 80 wt %based on the total weight of said composition.
 3. The method of claim 2,wherein the amount of said compound is from about 1 wt % to about 30 wt%, based on the total weight of said composition.
 4. The method of claim1, wherein the compound of Formula I is selected from the groupconsisting of menthol propyleneglycol-carbonate and isopulegolpropyleneglycol-carbonate, said compound being in enantiomerically pureform or in racemic form.
 5. The method of claim 1, wherein the compoundof Formula I is racemic menthol propyleneglycol-carbonate.
 6. The methodof claim 1, wherein the compound of Formula I is isopulegolpropyleneglycol-carbonate.
 7. The method of claim 1 wherein said site isthe integument of at least one living animal.
 8. The method of claim 7wherein said at least one living animal comprises humans.
 9. The methodof claim 7, wherein said at least one living animal comprises livestock.10. The method of claim 7, wherein said site is the integument of aplant, plant part or seed.
 11. An insect repellent compositioncomprising a compound of the formula:

wherein R represents a straight or branched chain, substituted orunsubstituted lower alkyl radical, or a straight or branched chain,substituted or unsubstituted lower alkenyl radical; X represents acarbonyl linking group (—C(═O)—) or a valence bond; n is 0 or 1; and R′represents a radical selected from the group consisting of substitutedor unsubstituted hydroxyalkyloxy and substituted or unsubstitutedhydroxyalkyl, when n is 1; and R′ represents an alkylamine radical whenn is 0; and a sustained release carrier.
 12. The composition of claim11, wherein said carrier is in the form of microtubles comprisinghalloysite clay.
 13. A cosmetic or personal care composition, selectedfrom the group of a perfume, cologne, deodorant, anti-perspirant, skincream, soap, shampoo, hair conditioner, hair rinse, bath oil, talc,sunblock or sunscreen, said composition comprising a compound of theformula:

wherein R represents a straight or branched chain, substituted orunsubstituted lower alkyl radical, or a straight or branched chain,substituted or unsubstituted lower alkenyl radical; X represents acarbonyl linking group (—C(═O)—) or a valence bond; n is 0 or 1; and R′represents a radical selected from the group consisting of substitutedor unsubstituted hydroxyalkyloxy and substituted or unsubstitutedhydroxyalkyl, when n is 1; and R′ represents an alkylamine radical whenn is
 0. 14. A household cleaning composition selected from the group ofa cleanser, detergent, fabric softener or air freshener, saidcomposition comprising a compound of the formula:

wherein R represents a straight or branched chain, substituted orunsubstituted lower alkyl radical, or a straight or branched chain,substituted or unsubstituted lower alkenyl radical; X represents acarbonyl linking group (—C(═O)—) or a valence bond; n is 0 or 1; and R′represents a radical selected from the group consisting of substitutedor unsubstituted hydroxyalkyloxy and substituted or unsubstitutedhydroxyalkyl, when n is 1; and R′ represents an alkylamine radical whenn is
 0. 15. An article of manufacture in the form of a fabric in whichis incorporated a compound of the formula:

wherein R represents a straight or branched chain, substituted orunsubstituted lower alkyl radical, or a straight or branched chain,substituted or unsubstituted lower alkenyl radical; X represents acarbonyl linking group (—C(═O)—) or a valence bond; n is 0 or 1; and R′represents a radical selected from the group consisting of substitutedor unsubstituted hydroxyalkyloxy and substituted or unsubstitutedhydroxyalkyl, when n is 1; and R′ represents an alkylamine radical whenn is
 0. 16. The article of claim 15, wherein said fabric is a non-woven,woven or knit fabric.
 17. The article of claim 15, wherein said fabricis mosquito netting.
 18. A method of rendering a fabric insectrepellent, said method comprising incorporating into said fabric acompound of the formula:

wherein R represents a straight or branched chain, substituted orunsubstituted lower alkyl radical, or a straight or branched chain,substituted or unsubstituted lower alkenyl radical; X represents acarbonyl linking group (—C(═O)—) or a valence bond; n is 0 or 1; and R′represents a radical selected from the group consisting of substitutedor unsubstituted hydroxyalkyloxy and substituted or unsubstitutedhydroxyalkyl, when n is 1; and R′ represents an alkylamine radical whenn is
 0. 19. The method of claim 18, wherein said compound isincorporated into said fabric by spraying, impregnation or padding. 20.A coating composition comprising a compound of the formula:

wherein R represents a straight or branched chain, substituted orunsubstituted lower alkyl radical, or a straight or branched chain,substituted or unsubstituted lower alkenyl radical; X represents acarbonyl linking group (—C(═O)—) or a valence bond; n is 0 or 1; and R′represents a radical selected from the group consisting of substitutedor unsubstituted hydroxyalkyloxy and substituted or unsubstitutedhydroxyalkyl, when n is 1; and R′ represents an alkylamine radical whenn is 0; and a synthetic polymer film former.
 21. A method for protectingan inanimate surface from infestation by insect pests said methodcomprising applying to said surface a coating composition comprising acompound of the formula:

wherein R represents a straight or branched chain, substituted orunsubstituted lower alkyl radical, or a straight or branched chain,substituted or unsubstituted lower alkenyl radical; X represents acarbonyl linking group (—C(═O)—) or a valence bond; n is 0 or 1; and R′represents a radical selected from the group consisting of substitutedor unsubstituted hydroxyalkyloxy and substituted or unsubstitutedhydroxyalkyl, when n is 1; and R′ represents an alkylamine radical whenn is O.
 22. The method according to claim 18, wherein said coatingcomposition is applied to said surface by brushing, spraying or dipping.